Homeodomain-interacting protein kinase HIPK4 regulates phosphorylation of manchette protein RIMBP3 during spermiogenesis
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
Nonobstructive azoospermia (NOA) is the most serious form of spermatogenesis abnormalities in male infertility. Genetic factors are important to consider as elements leading to NOA. Although many pathogenic genes have been reported, the causative genes of NOA for many patients are still unknown. In this study, we found ten point mutations in the gene encoding homeodomain-interacting protein kinase 4 (HIPK4) in patients with NOA, and using in vitro studies, we determined a premature termination point mutation (p. Lys490∗, c.1468A>T) that can cause decreased expression of HIPK4. Our phosphoproteomic analysis of Hipk4-/- testes revealed phosphorylation of multiple proteins regulated by HIPK4 during spermiogenesis. We also confirmed that a substrate of HIPK4 with four downregulated phosphorylation sites matching the xSPx motif is the known manchette-related protein RIMS-binding protein 3, which is required for sperm head morphogenesis. Therefore, we conclude HIPK4 regulates the phosphorylation of manchette protein RIMS-binding protein 3 and plays essential roles in sperm head shaping and male fertility.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:298 |
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| Enthalten in: |
The Journal of biological chemistry - 298(2022), 9 vom: 15. Sept., Seite 102327 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Xiaofei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.09.2022 Date Revised 18.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jbc.2022.102327 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM344505944 |
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| 100 | 1 | |a Liu, Xiaofei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Homeodomain-interacting protein kinase HIPK4 regulates phosphorylation of manchette protein RIMBP3 during spermiogenesis |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Nonobstructive azoospermia (NOA) is the most serious form of spermatogenesis abnormalities in male infertility. Genetic factors are important to consider as elements leading to NOA. Although many pathogenic genes have been reported, the causative genes of NOA for many patients are still unknown. In this study, we found ten point mutations in the gene encoding homeodomain-interacting protein kinase 4 (HIPK4) in patients with NOA, and using in vitro studies, we determined a premature termination point mutation (p. Lys490∗, c.1468A>T) that can cause decreased expression of HIPK4. Our phosphoproteomic analysis of Hipk4-/- testes revealed phosphorylation of multiple proteins regulated by HIPK4 during spermiogenesis. We also confirmed that a substrate of HIPK4 with four downregulated phosphorylation sites matching the xSPx motif is the known manchette-related protein RIMS-binding protein 3, which is required for sperm head morphogenesis. Therefore, we conclude HIPK4 regulates the phosphorylation of manchette protein RIMS-binding protein 3 and plays essential roles in sperm head shaping and male fertility | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a manchette | |
| 650 | 4 | |a phosphorylation | |
| 650 | 4 | |a protein kinase | |
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| 650 | 4 | |a spermatogenesis | |
| 650 | 4 | |a testis | |
| 650 | 7 | |a Codon, Nonsense |2 NLM | |
| 650 | 7 | |a Cytoskeletal Proteins |2 NLM | |
| 650 | 7 | |a RIMBP3 protein, human |2 NLM | |
| 650 | 7 | |a HIPK4 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
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| 700 | 1 | |a Zang, Chunyan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yifei |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Ru |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xiaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yueshuai |e verfasserin |4 aut | |
| 700 | 1 | |a Situ, Chenghao |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zhibin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Xuejiang |e verfasserin |4 aut | |
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